1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied a...1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied any history of hepatitis,hypertension,diabetes,cardiovascular disease,or other significant conditions.The patient was diagnosed with external auditory canal cholesteatoma and subsequently underwent canalplasty under general anesthesia.Routine anesthetic drugs,including 2%lidocaine,dexamethasone,propofol,sufentanil,rocuronium bromide,ondansetron,flurbiprofen axetil,neostigmine,and atropine,were used during surgery and anesthesia recovery.No significant events were noted,and the patient experienced only a blood loss of 10 mL.展开更多
As the integration of medical big data and artificial intelligence advances,the secure sharing of medical data has become a key driving force for advancing disease research and clinical diagnosis.Federated learning,a ...As the integration of medical big data and artificial intelligence advances,the secure sharing of medical data has become a key driving force for advancing disease research and clinical diagnosis.Federated learning,a distributed approach enabling collaborative data processing without sharing raw data,offers promising solutions to challenges in multi-center medical data sharing.This review summarizes the progress of federated learning in multi-center medical data processing,analyzed from four perspectives:system architectures,data distribution strategies,clinical tasks,and algorithmic models.At the same time,this paper explores the challenges in practical applications,such as data heterogeneity,communication overhead,and privacy concerns.It proposes driving future research development by optimizing algorithms,strengthening privacy protection mechanisms,and enhancing computational efficiency.展开更多
BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesi...BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesion kinase(FAK)has been implicated in regulating HSC glycolysis,its precise role in activation remains unclear.AIM To investigate the effects of FAK and fructose-1,6-bisphosphatase 1(FBP1)on LF through the modulation of aerobic glycolysis in HSCs.METHODS Eighteen mice were randomly assigned to three groups:Control,carbon tetrachloride(CCl_(4))-induced LF,and CCl_(4)with FAK inhibitor treatment.Liver tissues were analyzed using transcriptomic and proteomic sequencing.Differential gene expression,Mfuzz clustering,and protein interaction network analyses identified key regulatory factors.Immunohistochemistry(IHC)and Western blot(WB)analysis were used to assess FAK and FBP1 expression,along with glycolysis-related enzymes.The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.RESULTS Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl_(4)-induced fibrosis,which was restored upon FAK inhibition.Histological staining(hematoxylin and eosin,Masson’s trichrome,Sirius red)confirmed reduced fibrosis following FAK inhibition.WB analysis demonstrated suppression of glycolysisrelated enzymes.In LX-2 cells,FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1.Exogenous recombinant FBP1 inhibited HSC activation and glycolysis.Transwell and scratch assays showed that FBP1 significantly impaired HSC migration.In addition,WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.CONCLUSION FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs,thereby improving LF.Thus,FAK and FBP1 may be potential targets for LF treatment.展开更多
Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression ...Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis(RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA(STR/Ort)mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OAassociated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.展开更多
Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an ox...Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.展开更多
Background: Domestic violence is a pattern of assault and behavior perpetrated by one partner against the other. Historically most of those oppressed by domestic violence have been women. The lifetime prevalence of do...Background: Domestic violence is a pattern of assault and behavior perpetrated by one partner against the other. Historically most of those oppressed by domestic violence have been women. The lifetime prevalence of domestic violence against women is 10% - 69%. Though this violence might have started or escalated during pregnancy, pregnancy specific prevalence is between 1% - 20%. The objective was to determine the prevalence and obstetric complications. Domestic violence is against pregnant women in tertiary clinic of a developing nation. Methodology: It was a hospital based cross-sectional case control study conducted within the period of one year. Close ended questionnaires were administered. Result: Two hundred and seventy patients were recruited. The lifetime prevalence of physical violence against women was 28.5%. 12.5% (5/40) of victims smoke cigarettes;the prevalence of alcohol intake by the victims was 45%. 72.5% of partners of victims smoke as compared to 25.5% of partners of non victims. Unemployed women were victims of domestic violence far more than the employed women. Pregnant women who are victims of physical violence are more likely to suffer adverse pregnancy outcome. Violence in pregnancy is quite commoner than most of the conditions routinely screened for during antenatal care. The association of such violence with significant maternal and fetal/neonatal morbidity and mortality emphasizes the fact that domestic violence is not just a social problem but a feto-maternal health hazard that requires the input of every stakeholder to address.展开更多
AIM:To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy(PDT)among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang ...AIM:To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy(PDT)among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014.METHODS:Study subjects were recruited retrospectively using the Electronic Medical Record(EMR)database software in Hospital Selayang.Demographic data,medical history,diagnostic procedure,treatments and diagnosis of patients were recorded.RESULTS:The five-year analysis included 821 patients with a mean age of 65.9±11.73 y.Overall,there were a highernumber of males(63.1%)and a higher number of Chinese(47.4%)patients.Among the 821 patients,62.9%received ranibizumab injection followed by 19.2%PDT therapy and 17.9%had ranibizumab combined with PDT therapy.Age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)were the most common retinal eye diseases reported,recording prevalence of 25.0%and 45.6%,respectively.The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014.In terms of treatment,following multiple logistic regression,AMD was associated with the subjects being more likely to have received ranibizumab monotherapy(P〈0.001)while PCV was associated with more likely to have received PDT(P〈0.001)and PDT combined with ranibizumab therapy(P〈0.001).CONCLUSION:The tertiary care setting in Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD,while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.展开更多
A 30 years old grandmultiparous woman presented with 6 month history of severe abdominal pain and 4 month history of progressive abdominal swelling associated with multiple swellings on her abdomen and her breasts. Sh...A 30 years old grandmultiparous woman presented with 6 month history of severe abdominal pain and 4 month history of progressive abdominal swelling associated with multiple swellings on her abdomen and her breasts. She had laparotomy two years earlier for a suspected fibroid. A repeat laparatomy discovered a huge left ovarian tumour;which are multilobulated and hard. She had Total Abdominal Hysterectomy and Salpingectomy with Lumpectomy on both breast. Histology report turned out as Dysgerminoma, breast, Subcutaneous Tissue and Skin Metastatic Dysgerminoma.展开更多
This article discusses the original article published by Lu et al in the latest issue.The article confirmed through a cohort study the clinical efficacy of the triple live bacteria of Bifidobacterium combined with mir...This article discusses the original article published by Lu et al in the latest issue.The article confirmed through a cohort study the clinical efficacy of the triple live bacteria of Bifidobacterium combined with mirtazapine in treating postoperative depression of gastric cancer patients,also explored the multi-target therapeutic mechanisms of Bifidobacterium triple viable bacteria combined with mirtazapine in managing depression in patients after radical gastrectomy for gastric cancer for the first time.The results indicated that Bifidobacterium could alleviate depression in patients after radical gastrectomy for gastric cancer.Gastric cancer patients undergoing surgery frequently experience postoperative psychological disorders,notably depression.These conditions not only impair quality of life but also negatively impact disease-free and overall survival.This editorial explores the underestimated psychological challenges following gastric cancer surgery,including depression,anxiety,adjustment disorders,and post-traumatic stress disorder.It further examines the therapeutic potential of Bifidobacterium triple viable probiotics,combined with mirtazapine,in alleviating postoperative depression through microbiological,immunological,and neurological mechanisms.Clinical evidence highlights additional benefits,such as improved gastrointestinal function,enhanced immunity,and better nutritional status,underscoring a holistic approach to postoperative care.While promising,further large-scale trials are needed to optimize and personalize probiotic-based interventions.展开更多
Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechani...Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechanism of action using molecular modeling. Methods: Three different human carcinoma cell lines were used namely hepatocyte carcinoma (HEPG2), breast adenocarcinoma (MCF7) and colon cancer (HCT116). Molecular docking simulations for tested thiazole analogue and its virtual analogues against the cytochrome P-450 2A6 enzyme and mutated SOD were performed. Results: Cell lines cytotoxicity revealed that the tested thiazole analogue exerts a significant anti-proliferative activity in all the used human carcinoma cell lines with a pronounced anti-proliferative effect in liver carcinoma cell line HEPG2 (IC50 = 23.8 μg/ml) whereas the anti-proliferative effect in colon carcinoma and breast cancer cell lines was poor with IC50 = 50 μg/ml and IC50 > 50 μg/ml respectively. The postulated mechanism of action revealed the high affinity to inhibit SOD and CYP2A6 enzymes in the liver. Conclusion: The thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl)thiazole) is a potential liver specific anticancer agent capable of interfering with both apoptotic signaling pathway and the free radical processing in liver which leads to more studies on liver cancer from different perspective rather than the apoptotic signaling pathway.展开更多
To compare the surgical managements for ectopic pregnancy Methods In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients Results The chan...To compare the surgical managements for ectopic pregnancy Methods In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients Results The change from laparotomy to laparoscopic treatment was significant The success rates of salpingostomy and salpingectomy under laparoscopy or laparotomy were 100% No serious complications occurred The operation time and length of hospital stay for laparoscopic salpingostomy were shorter than those for laparotomy with salpingostomy Conclusion Laparoscopic salpingostomy and laparoscopic salpingectomy are better than laparotomy in the treatment of ectopic pregnancy展开更多
Background Recent studies showed that bone marrow-derived mesenchymal stem ceils （BMSCs） had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 ...Background Recent studies showed that bone marrow-derived mesenchymal stem ceils （BMSCs） had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 （GDF-6） on the tenogenic differentiation of BMSCs in vitro, and then combined with small intestine submucous （SIS） to promote tendon regeneration in vivo. Methods The BMSCs were isolated from the green fluorescent protein （GFP） rats, and were characterized by multi-differentiation assays following our previous study protocol. BMSCs cultured with different concentrations of GDF-6, without growth factors served as control. After 2 weeks, mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6. Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P 〈0.05 was regarded as statistically significant. The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model, the BMSCs combined with SIS served as control. After 12 and 4 weeks in nude mice and tendon injury model, the samples were collected for histology. Results After the BMSCs were treated with different concentration of GDF-6 for 2 weeks, the fold changes of the specific markers （Tenomodulin and Scleraxis） mRNA expression were significantly higher in GDF-6 （20 ng/ml） group （P 〈_0.05）, which was also confirmed by Western blotting result. The BMSCs became parallel in orientation after GDF-6 （20 ng/ml） treatment, but the BMSCs in control group were randomly oriented. The GDF-6 （20 ng/ml） treated BMSCs were combined with SIS, and were implanted in nude mice for 12 weeks, the histology showed neo-tendon formation. In the SD rat patellar tendon window injury model, the histology also indicated the GDF-6 （20 ng/ml） treated BMSCs combined with SIS could promote tendon regeneration. Conclusions GDF-6 has tenogenic effect on the tenogenic differentiation of BMSCs, and GDF-6 （20 ng/ml） has better tenogenic effect compared to other concentrations. The GDF-6 （20 ng/ml） treated BMSCs combined with SIS can form neo-tendons and promote tendon regeneration.展开更多
In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges l...In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges like poor biocompatibility,premature drug release,suboptimal targeting to infection sites and short blood circulation time are still challenging.To achieve targeted drug delivery and enhance antibacterial activity,here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin(PEG-Schiff-Van)prodrug and free Van in one drug delivery system.The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition.Notably,on account of the combination of physical encapsulation and chemical conjugation of vancomycin,these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior,which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period.In addition,more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity.Using this strategy,this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites,thereby presenting prominent antibacterial therapy both in vitro and in vivo.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be a promising class of antimicrobial materials for potential clinical translation.展开更多
The effect of immune‐based therapies on patients with epidermal growth factor receptor(EGFR)-positive advanced non-small cell lung cancer(NSCLC)resistant to EGFR tyrosine kinase inhibitor(TKI)therapy remains unclear....The effect of immune‐based therapies on patients with epidermal growth factor receptor(EGFR)-positive advanced non-small cell lung cancer(NSCLC)resistant to EGFR tyrosine kinase inhibitor(TKI)therapy remains unclear.The ALTER-L038 study aimed to evaluate efficacy and safety of a chemotherapy-free combination of benmelstobart,an anti-programmed cell death ligand 1 antibody,and anlotinib,a small-molecule multi-target anti-angiogenic TKI,in EGFR-positive advanced NSCLC patients who progressed after EGFR TKI therapy.Patients were enrolled in a phase I/II study.In phase I(dose-escalation),patients received anlotinib(8,10,12 mg)plus benmelstobart(1200 mg).Recommended phase II dose,determined during phase I,was used in phase II dose-expansion cohort.Primary endpoints were maximum tolerable dose in phase I and progression-free survival(PFS)in phase II.At the data cutoff date(March 10,2024),55 patients were enrolled in phase II dose-expansion cohort.Median PFS of patients included in phase II cohort was 9.0 months,median overall survival was 28.9 months,objective response rate was 25.5%,disease control rate was 87.3%,and median duration of response was 19.8 months.Incidence of grade≥3 treatment-related adverse events in study population was 25.5%(14/55),whereas grade≥3 immune-related adverse events occurred in 10.9%(6/55)of patients.Benmelstobart plus anlotinib showed promising anti-tumor efficacy with tolerable safety profile,supporting the value of further development of this convenient chemotherapy-free regimen for patients with EGFR-positive advanced NSCLC who progressed after EGFR TKI therapy.Trial Registration:ChiCTR1900026273.展开更多
Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 i...Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.展开更多
COVID-19 has been an emerging and rapidly evolving risk to people of the world in 2020.Facing this dangerous situation,many colleagues in Neurorestoratology did their best to avoid infection if themselves and their pa...COVID-19 has been an emerging and rapidly evolving risk to people of the world in 2020.Facing this dangerous situation,many colleagues in Neurorestoratology did their best to avoid infection if themselves and their patients,and continued their work in the research areas described in the 2020 Yearbook of Neurorestoratology.Neurorestorative achievements and progress during 2020 includes recent findings on the pathogenesis of neurological diseases,neurorestorative mechanisms and clinical therapeutic achievements.Therapeutic progress during this year included advances in cell therapies,neurostimulation/neuromodulation,brain-computer interface(BCI),and pharmaceutical neurorestorative therapies,which improved neurological functions and quality of life for patients.Four clinical guidelines or standards of Neurorestoratology were published in 2020.Milestone examples include:1)a multicenter randomized,double-blind,placebo-controlled study of olfactory ensheathing cell treatment of chronic stroke showed functional improvements;2)patients after transhumeral amputation experienced increased sensory acuity and had improved effectiveness in work and other activities of daily life using a prosthesis;3)a patient with amyotrophic lateral sclerosis used a steady-state visual evoked potential(SSVEP)-based BCI to achieve accurate and speedy computer input;4)a patient with complete chronic spinal cord injury recovered both motor function and touch sensation with a BCI and restored ability to detect objects by touch and several sensorimotor functions.We hope these achievements motivate and encourage other scientists and physicians to increase neurorestorative research and its therapeutic applications.展开更多
Purpose: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (A RMD) over 1 year. Methods: The consecutive interventional c...Purpose: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (A RMD) over 1 year. Methods: The consecutive interventional case series included 5 6 patients with exudative ARMD. During vitrectomy the submacular neovascular mem brane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, w ere injected into the submacular space. Included were patients with subfoveal oc cult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigme nt epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome me asures were visual acuity, foveal fixation, size of CNV and rate of recurrence b ased on fluorescence angiographic imaging. Results: All patients underwent succe ssful surgical removal of the CNV with consecutive subretinal IPE injection. Vis ual acuity was better than 20/100 in 19 patients preoperatively and in 18 patien ts postoperatively. A visual acuity of 20/100 or less was found in 37 patients p reoperatively and in 38 patients postoperatively. Mean preoperative visual acuit y (1.0±0.3 logMAR units) did not change significantly after 1 year (1.0±0.3 lo gMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgica lly denuded area could be demonstrated in 25 eyes (45%). Conclusions: Autologou s IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasi ble with a low rate of complications. Continued research seems justified to impr ove functional outcome.展开更多
Aims: To determine whether central corneal thickness (CCT) is a significant pr edictor of visual field and optic disc progression in open angle glaucoma. Metho ds: Data were obtained from a prospective study of glauco...Aims: To determine whether central corneal thickness (CCT) is a significant pr edictor of visual field and optic disc progression in open angle glaucoma. Metho ds: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 month s. Progression was determined using a trend based approach called evidence of ch ange (EOC) analysis in which sectoral ordinal scores based on the significance o f regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using t he event based glaucoma change probability (GCP) analysis using both total and p attern deviation. Results: The sample contained 101 eyes of 54 patients (mean (S D) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseli ne visual fields and lower mean IOP in the follow up. In the longitudinal analys is CCT was not correlated with the EOC scores for visual field or optic disc cha nge. In the GCP analyses, there was a tendency for groups classified as progress ing to have lower CCT compared to nonprogressing groups. In a multivariate analy ses accounting for IOP, the opposite was found, whereby higher CCT was associate d with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with establi shed glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.展开更多
Immune checkpoint blockade(ICB)therapy,which has revolutionized cancer treatment,has been approved for the treatment of triple-negative breast cancer(TNBC).Unfortunately,most patients with TNBC are either not eligible...Immune checkpoint blockade(ICB)therapy,which has revolutionized cancer treatment,has been approved for the treatment of triple-negative breast cancer(TNBC).Unfortunately,most patients with TNBC are either not eligible for treatment or exhibit resistance,resulting in limited overall survival benefits.There is an urgent need to elucidate the mechanisms of resistance and enhance therapeutic efficacy.Here,via CRISPR activation(CRISPRa)screening,we identified family with sequence similarity 114 member A1(FAM114A1)as a key mediator of immune evasion and ICB resistance in TNBC.Mechanistically,FAM114A1 binds p85αto disrupt the p85α/p110αprotein complex,thus activating the PI3K/AKT pathway and simultaneously preventing condensate formation of E2F Transcription Factor 4(E2F4)to promote E2F4-driven Metadherin(MTDH)transcription.Upregulation of these FAM114A1-mediated pathways suppresses tumor antigen presentation and consequently attenuates antitumor immunity in TNBC.Moreover,targeting FAM114A1 improves the therapeutic effectiveness of anti-PD-1 therapy in mouse models,and a FAM114A1-based signature shows strong predictive performance for identifying patients with TNBC who may benefit from ICB.Collectively,our findings not only reveal that FAM114A1 is an immune evasion driver but also highlight it as a promising biomarker and therapeutic target.Our study provides new insights into TNBC immune evasion and outlines a potential avenue to improve the effectiveness of ICB.展开更多
Titanium(Ti)and its alloy implants often face issues such as insufficient tissue adhesion and vulnerability of the bio inert surface.Given that the long-term stability of implants depends on their perfect integration ...Titanium(Ti)and its alloy implants often face issues such as insufficient tissue adhesion and vulnerability of the bio inert surface.Given that the long-term stability of implants depends on their perfect integration with the surrounding tissues to withstand various environmental stresses,current research mainly focuses on mimicking the structure of the extracellular matrix.The aim is to promote bone tissue formation through regulation of the immune response by metal ions,thereby enhancing the effectiveness of tissue integration.The self-assembled zinc(Zn)-doped hydroxyapatite nanoparticles(nHA)with polydopamine(PDA)and copper ions(Cu^(2+))was deposited onto the alkali treated Ti surface to fabricate the P-Zn-Cu/Ti coating.The so-constructed multifunc-tional coating with bionic micro/nano-structures on the Ti surface can achieve the sequential release of Cu^(2+)and zinc ions(Zn^(2+))through the rapid release of Cu^(2+)in the early stage and the slow release of Zn^(2+),and followed the functional characteristics of sequentially regulating antibacterial,immune,and osteogenic responses.This study presents a promising strategy to address the challenges associated with the failure of Ti implants,thus promoting the development of implant technology and improving clinical efficacy.展开更多
基金supported by grants from Young Scientists Fund of the National Natural Science Foundation of China(grant number.82301295).
文摘1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied any history of hepatitis,hypertension,diabetes,cardiovascular disease,or other significant conditions.The patient was diagnosed with external auditory canal cholesteatoma and subsequently underwent canalplasty under general anesthesia.Routine anesthetic drugs,including 2%lidocaine,dexamethasone,propofol,sufentanil,rocuronium bromide,ondansetron,flurbiprofen axetil,neostigmine,and atropine,were used during surgery and anesthesia recovery.No significant events were noted,and the patient experienced only a blood loss of 10 mL.
基金supported and funded by the National Natural Science Foundation of China(82101079)the Key R&D Program of Jiangsu Province(BE2023836)the National Key Research and Development Program of China(SQ2023YFC2400025).
文摘As the integration of medical big data and artificial intelligence advances,the secure sharing of medical data has become a key driving force for advancing disease research and clinical diagnosis.Federated learning,a distributed approach enabling collaborative data processing without sharing raw data,offers promising solutions to challenges in multi-center medical data sharing.This review summarizes the progress of federated learning in multi-center medical data processing,analyzed from four perspectives:system architectures,data distribution strategies,clinical tasks,and algorithmic models.At the same time,this paper explores the challenges in practical applications,such as data heterogeneity,communication overhead,and privacy concerns.It proposes driving future research development by optimizing algorithms,strengthening privacy protection mechanisms,and enhancing computational efficiency.
基金Supported by the Science and Technology Program of the Guizhou Province,No.[2021]094National Natural Science Foundation of China,No.82060116 and No.82260129+1 种基金Guizhou Provincial Science and Technology Program,No.QKHJC-ZK[2023]214Doctoral Research Start-up Fund Project of Guizhou Medical University,No.gyfybsky[2021]63.
文摘BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesion kinase(FAK)has been implicated in regulating HSC glycolysis,its precise role in activation remains unclear.AIM To investigate the effects of FAK and fructose-1,6-bisphosphatase 1(FBP1)on LF through the modulation of aerobic glycolysis in HSCs.METHODS Eighteen mice were randomly assigned to three groups:Control,carbon tetrachloride(CCl_(4))-induced LF,and CCl_(4)with FAK inhibitor treatment.Liver tissues were analyzed using transcriptomic and proteomic sequencing.Differential gene expression,Mfuzz clustering,and protein interaction network analyses identified key regulatory factors.Immunohistochemistry(IHC)and Western blot(WB)analysis were used to assess FAK and FBP1 expression,along with glycolysis-related enzymes.The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.RESULTS Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl_(4)-induced fibrosis,which was restored upon FAK inhibition.Histological staining(hematoxylin and eosin,Masson’s trichrome,Sirius red)confirmed reduced fibrosis following FAK inhibition.WB analysis demonstrated suppression of glycolysisrelated enzymes.In LX-2 cells,FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1.Exogenous recombinant FBP1 inhibited HSC activation and glycolysis.Transwell and scratch assays showed that FBP1 significantly impaired HSC migration.In addition,WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.CONCLUSION FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs,thereby improving LF.Thus,FAK and FBP1 may be potential targets for LF treatment.
基金supported by the NIH/NIAMS grants AR071432 and AR063943 (to X.C.)
文摘Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis(RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA(STR/Ort)mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OAassociated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.
文摘Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.
文摘Background: Domestic violence is a pattern of assault and behavior perpetrated by one partner against the other. Historically most of those oppressed by domestic violence have been women. The lifetime prevalence of domestic violence against women is 10% - 69%. Though this violence might have started or escalated during pregnancy, pregnancy specific prevalence is between 1% - 20%. The objective was to determine the prevalence and obstetric complications. Domestic violence is against pregnant women in tertiary clinic of a developing nation. Methodology: It was a hospital based cross-sectional case control study conducted within the period of one year. Close ended questionnaires were administered. Result: Two hundred and seventy patients were recruited. The lifetime prevalence of physical violence against women was 28.5%. 12.5% (5/40) of victims smoke cigarettes;the prevalence of alcohol intake by the victims was 45%. 72.5% of partners of victims smoke as compared to 25.5% of partners of non victims. Unemployed women were victims of domestic violence far more than the employed women. Pregnant women who are victims of physical violence are more likely to suffer adverse pregnancy outcome. Violence in pregnancy is quite commoner than most of the conditions routinely screened for during antenatal care. The association of such violence with significant maternal and fetal/neonatal morbidity and mortality emphasizes the fact that domestic violence is not just a social problem but a feto-maternal health hazard that requires the input of every stakeholder to address.
基金Supported by Putra Grant from Universiti Putra Malaysia(No.9409800,No.9432700)
文摘AIM:To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy(PDT)among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014.METHODS:Study subjects were recruited retrospectively using the Electronic Medical Record(EMR)database software in Hospital Selayang.Demographic data,medical history,diagnostic procedure,treatments and diagnosis of patients were recorded.RESULTS:The five-year analysis included 821 patients with a mean age of 65.9±11.73 y.Overall,there were a highernumber of males(63.1%)and a higher number of Chinese(47.4%)patients.Among the 821 patients,62.9%received ranibizumab injection followed by 19.2%PDT therapy and 17.9%had ranibizumab combined with PDT therapy.Age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)were the most common retinal eye diseases reported,recording prevalence of 25.0%and 45.6%,respectively.The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014.In terms of treatment,following multiple logistic regression,AMD was associated with the subjects being more likely to have received ranibizumab monotherapy(P〈0.001)while PCV was associated with more likely to have received PDT(P〈0.001)and PDT combined with ranibizumab therapy(P〈0.001).CONCLUSION:The tertiary care setting in Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD,while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.
文摘A 30 years old grandmultiparous woman presented with 6 month history of severe abdominal pain and 4 month history of progressive abdominal swelling associated with multiple swellings on her abdomen and her breasts. She had laparotomy two years earlier for a suspected fibroid. A repeat laparatomy discovered a huge left ovarian tumour;which are multilobulated and hard. She had Total Abdominal Hysterectomy and Salpingectomy with Lumpectomy on both breast. Histology report turned out as Dysgerminoma, breast, Subcutaneous Tissue and Skin Metastatic Dysgerminoma.
文摘This article discusses the original article published by Lu et al in the latest issue.The article confirmed through a cohort study the clinical efficacy of the triple live bacteria of Bifidobacterium combined with mirtazapine in treating postoperative depression of gastric cancer patients,also explored the multi-target therapeutic mechanisms of Bifidobacterium triple viable bacteria combined with mirtazapine in managing depression in patients after radical gastrectomy for gastric cancer for the first time.The results indicated that Bifidobacterium could alleviate depression in patients after radical gastrectomy for gastric cancer.Gastric cancer patients undergoing surgery frequently experience postoperative psychological disorders,notably depression.These conditions not only impair quality of life but also negatively impact disease-free and overall survival.This editorial explores the underestimated psychological challenges following gastric cancer surgery,including depression,anxiety,adjustment disorders,and post-traumatic stress disorder.It further examines the therapeutic potential of Bifidobacterium triple viable probiotics,combined with mirtazapine,in alleviating postoperative depression through microbiological,immunological,and neurological mechanisms.Clinical evidence highlights additional benefits,such as improved gastrointestinal function,enhanced immunity,and better nutritional status,underscoring a holistic approach to postoperative care.While promising,further large-scale trials are needed to optimize and personalize probiotic-based interventions.
文摘Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechanism of action using molecular modeling. Methods: Three different human carcinoma cell lines were used namely hepatocyte carcinoma (HEPG2), breast adenocarcinoma (MCF7) and colon cancer (HCT116). Molecular docking simulations for tested thiazole analogue and its virtual analogues against the cytochrome P-450 2A6 enzyme and mutated SOD were performed. Results: Cell lines cytotoxicity revealed that the tested thiazole analogue exerts a significant anti-proliferative activity in all the used human carcinoma cell lines with a pronounced anti-proliferative effect in liver carcinoma cell line HEPG2 (IC50 = 23.8 μg/ml) whereas the anti-proliferative effect in colon carcinoma and breast cancer cell lines was poor with IC50 = 50 μg/ml and IC50 > 50 μg/ml respectively. The postulated mechanism of action revealed the high affinity to inhibit SOD and CYP2A6 enzymes in the liver. Conclusion: The thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl)thiazole) is a potential liver specific anticancer agent capable of interfering with both apoptotic signaling pathway and the free radical processing in liver which leads to more studies on liver cancer from different perspective rather than the apoptotic signaling pathway.
文摘To compare the surgical managements for ectopic pregnancy Methods In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients Results The change from laparotomy to laparoscopic treatment was significant The success rates of salpingostomy and salpingectomy under laparoscopy or laparotomy were 100% No serious complications occurred The operation time and length of hospital stay for laparoscopic salpingostomy were shorter than those for laparotomy with salpingostomy Conclusion Laparoscopic salpingostomy and laparoscopic salpingectomy are better than laparotomy in the treatment of ectopic pregnancy
文摘Background Recent studies showed that bone marrow-derived mesenchymal stem ceils （BMSCs） had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 （GDF-6） on the tenogenic differentiation of BMSCs in vitro, and then combined with small intestine submucous （SIS） to promote tendon regeneration in vivo. Methods The BMSCs were isolated from the green fluorescent protein （GFP） rats, and were characterized by multi-differentiation assays following our previous study protocol. BMSCs cultured with different concentrations of GDF-6, without growth factors served as control. After 2 weeks, mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6. Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P 〈0.05 was regarded as statistically significant. The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model, the BMSCs combined with SIS served as control. After 12 and 4 weeks in nude mice and tendon injury model, the samples were collected for histology. Results After the BMSCs were treated with different concentration of GDF-6 for 2 weeks, the fold changes of the specific markers （Tenomodulin and Scleraxis） mRNA expression were significantly higher in GDF-6 （20 ng/ml） group （P 〈_0.05）, which was also confirmed by Western blotting result. The BMSCs became parallel in orientation after GDF-6 （20 ng/ml） treatment, but the BMSCs in control group were randomly oriented. The GDF-6 （20 ng/ml） treated BMSCs were combined with SIS, and were implanted in nude mice for 12 weeks, the histology showed neo-tendon formation. In the SD rat patellar tendon window injury model, the histology also indicated the GDF-6 （20 ng/ml） treated BMSCs combined with SIS could promote tendon regeneration. Conclusions GDF-6 has tenogenic effect on the tenogenic differentiation of BMSCs, and GDF-6 （20 ng/ml） has better tenogenic effect compared to other concentrations. The GDF-6 （20 ng/ml） treated BMSCs combined with SIS can form neo-tendons and promote tendon regeneration.
基金supported by Youth Innovation Promotion Association CAS(2019031)National Natural Science Foundation of China(51973226,81972081 and 21604093)+3 种基金China Postdoctoral Science Foundation(2020M683733)Military Medical Science and Technology Youth Cultivation Project(20QNPY109)Military Medical Youth Growth Program of PLA General Hospital(QNC19028)Shanghai Changning Committee of Science and Technology of China(CNKW2020Y01).
文摘In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges like poor biocompatibility,premature drug release,suboptimal targeting to infection sites and short blood circulation time are still challenging.To achieve targeted drug delivery and enhance antibacterial activity,here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin(PEG-Schiff-Van)prodrug and free Van in one drug delivery system.The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition.Notably,on account of the combination of physical encapsulation and chemical conjugation of vancomycin,these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior,which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period.In addition,more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity.Using this strategy,this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites,thereby presenting prominent antibacterial therapy both in vitro and in vivo.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be a promising class of antimicrobial materials for potential clinical translation.
基金funded by the Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.,Jiangsu,China.
文摘The effect of immune‐based therapies on patients with epidermal growth factor receptor(EGFR)-positive advanced non-small cell lung cancer(NSCLC)resistant to EGFR tyrosine kinase inhibitor(TKI)therapy remains unclear.The ALTER-L038 study aimed to evaluate efficacy and safety of a chemotherapy-free combination of benmelstobart,an anti-programmed cell death ligand 1 antibody,and anlotinib,a small-molecule multi-target anti-angiogenic TKI,in EGFR-positive advanced NSCLC patients who progressed after EGFR TKI therapy.Patients were enrolled in a phase I/II study.In phase I(dose-escalation),patients received anlotinib(8,10,12 mg)plus benmelstobart(1200 mg).Recommended phase II dose,determined during phase I,was used in phase II dose-expansion cohort.Primary endpoints were maximum tolerable dose in phase I and progression-free survival(PFS)in phase II.At the data cutoff date(March 10,2024),55 patients were enrolled in phase II dose-expansion cohort.Median PFS of patients included in phase II cohort was 9.0 months,median overall survival was 28.9 months,objective response rate was 25.5%,disease control rate was 87.3%,and median duration of response was 19.8 months.Incidence of grade≥3 treatment-related adverse events in study population was 25.5%(14/55),whereas grade≥3 immune-related adverse events occurred in 10.9%(6/55)of patients.Benmelstobart plus anlotinib showed promising anti-tumor efficacy with tolerable safety profile,supporting the value of further development of this convenient chemotherapy-free regimen for patients with EGFR-positive advanced NSCLC who progressed after EGFR TKI therapy.Trial Registration:ChiCTR1900026273.
基金This study was funded by RemeGen Co.,Ltd.This work was also supported by the National Natural Science Foundation of China(No.91959205)the Ministry of Science and Technology of China(No.2017YFC1308900,No.2018ZX09201-015)Beijing Municipal Health Commission(No.2020-1-1022)。
文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.
文摘COVID-19 has been an emerging and rapidly evolving risk to people of the world in 2020.Facing this dangerous situation,many colleagues in Neurorestoratology did their best to avoid infection if themselves and their patients,and continued their work in the research areas described in the 2020 Yearbook of Neurorestoratology.Neurorestorative achievements and progress during 2020 includes recent findings on the pathogenesis of neurological diseases,neurorestorative mechanisms and clinical therapeutic achievements.Therapeutic progress during this year included advances in cell therapies,neurostimulation/neuromodulation,brain-computer interface(BCI),and pharmaceutical neurorestorative therapies,which improved neurological functions and quality of life for patients.Four clinical guidelines or standards of Neurorestoratology were published in 2020.Milestone examples include:1)a multicenter randomized,double-blind,placebo-controlled study of olfactory ensheathing cell treatment of chronic stroke showed functional improvements;2)patients after transhumeral amputation experienced increased sensory acuity and had improved effectiveness in work and other activities of daily life using a prosthesis;3)a patient with amyotrophic lateral sclerosis used a steady-state visual evoked potential(SSVEP)-based BCI to achieve accurate and speedy computer input;4)a patient with complete chronic spinal cord injury recovered both motor function and touch sensation with a BCI and restored ability to detect objects by touch and several sensorimotor functions.We hope these achievements motivate and encourage other scientists and physicians to increase neurorestorative research and its therapeutic applications.
文摘Purpose: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (A RMD) over 1 year. Methods: The consecutive interventional case series included 5 6 patients with exudative ARMD. During vitrectomy the submacular neovascular mem brane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, w ere injected into the submacular space. Included were patients with subfoveal oc cult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigme nt epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome me asures were visual acuity, foveal fixation, size of CNV and rate of recurrence b ased on fluorescence angiographic imaging. Results: All patients underwent succe ssful surgical removal of the CNV with consecutive subretinal IPE injection. Vis ual acuity was better than 20/100 in 19 patients preoperatively and in 18 patien ts postoperatively. A visual acuity of 20/100 or less was found in 37 patients p reoperatively and in 38 patients postoperatively. Mean preoperative visual acuit y (1.0±0.3 logMAR units) did not change significantly after 1 year (1.0±0.3 lo gMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgica lly denuded area could be demonstrated in 25 eyes (45%). Conclusions: Autologou s IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasi ble with a low rate of complications. Continued research seems justified to impr ove functional outcome.
文摘Aims: To determine whether central corneal thickness (CCT) is a significant pr edictor of visual field and optic disc progression in open angle glaucoma. Metho ds: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 month s. Progression was determined using a trend based approach called evidence of ch ange (EOC) analysis in which sectoral ordinal scores based on the significance o f regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using t he event based glaucoma change probability (GCP) analysis using both total and p attern deviation. Results: The sample contained 101 eyes of 54 patients (mean (S D) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseli ne visual fields and lower mean IOP in the follow up. In the longitudinal analys is CCT was not correlated with the EOC scores for visual field or optic disc cha nge. In the GCP analyses, there was a tendency for groups classified as progress ing to have lower CCT compared to nonprogressing groups. In a multivariate analy ses accounting for IOP, the opposite was found, whereby higher CCT was associate d with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with establi shed glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.
基金supported by grants from the National Natural Science Foundation of China(2021hwyq55 and 82472950 to M.Shen,32270745 to Y.Lu)the Natural Science Foundation of Shanghai(23ZR1466500 to Y.Lu)+1 种基金the Shanghai Municipal Health Commission(2022YQ067 to Y.Lu)supported by the Human Phenome Data Center of Fudan University。
文摘Immune checkpoint blockade(ICB)therapy,which has revolutionized cancer treatment,has been approved for the treatment of triple-negative breast cancer(TNBC).Unfortunately,most patients with TNBC are either not eligible for treatment or exhibit resistance,resulting in limited overall survival benefits.There is an urgent need to elucidate the mechanisms of resistance and enhance therapeutic efficacy.Here,via CRISPR activation(CRISPRa)screening,we identified family with sequence similarity 114 member A1(FAM114A1)as a key mediator of immune evasion and ICB resistance in TNBC.Mechanistically,FAM114A1 binds p85αto disrupt the p85α/p110αprotein complex,thus activating the PI3K/AKT pathway and simultaneously preventing condensate formation of E2F Transcription Factor 4(E2F4)to promote E2F4-driven Metadherin(MTDH)transcription.Upregulation of these FAM114A1-mediated pathways suppresses tumor antigen presentation and consequently attenuates antitumor immunity in TNBC.Moreover,targeting FAM114A1 improves the therapeutic effectiveness of anti-PD-1 therapy in mouse models,and a FAM114A1-based signature shows strong predictive performance for identifying patients with TNBC who may benefit from ICB.Collectively,our findings not only reveal that FAM114A1 is an immune evasion driver but also highlight it as a promising biomarker and therapeutic target.Our study provides new insights into TNBC immune evasion and outlines a potential avenue to improve the effectiveness of ICB.
基金supported by the National Natural Science Foundation of China(52071277)the key project of The General Hospital of Western Theater Command of PLA(GY-A-12).
文摘Titanium(Ti)and its alloy implants often face issues such as insufficient tissue adhesion and vulnerability of the bio inert surface.Given that the long-term stability of implants depends on their perfect integration with the surrounding tissues to withstand various environmental stresses,current research mainly focuses on mimicking the structure of the extracellular matrix.The aim is to promote bone tissue formation through regulation of the immune response by metal ions,thereby enhancing the effectiveness of tissue integration.The self-assembled zinc(Zn)-doped hydroxyapatite nanoparticles(nHA)with polydopamine(PDA)and copper ions(Cu^(2+))was deposited onto the alkali treated Ti surface to fabricate the P-Zn-Cu/Ti coating.The so-constructed multifunc-tional coating with bionic micro/nano-structures on the Ti surface can achieve the sequential release of Cu^(2+)and zinc ions(Zn^(2+))through the rapid release of Cu^(2+)in the early stage and the slow release of Zn^(2+),and followed the functional characteristics of sequentially regulating antibacterial,immune,and osteogenic responses.This study presents a promising strategy to address the challenges associated with the failure of Ti implants,thus promoting the development of implant technology and improving clinical efficacy.
